Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.
Introduction: The free androgen index (FAI) values differ among patients with polycystic ovarian syndrome; however, the differences are not fully understood or known. The aim of the study was to evaluate FAI in women with polycystic ovary syndrome (PCOS) in regard to the phenotype of the PCOS and insulin resistance status. Material and methods: Anthropometric, hormonal, and biochemical parameters were assessed in 312 recruited women with PCOS. The FAI values were calculated in the reproductive and metabolic phenotypes of PCOS in groups of insulin resistance status based on the homeostasis model assessment-insulin resistance (HOMA-IR) > 2.0 or fasting insulin (FI) > 10 mmol/L. To test the relationship between individual variables, Spearman's correlation analysis, the Kolmogorov-Smirnov test, and Student's t-test were used. Results: The correlation between FAI values and HOMA-IR and FI was 0.42 and 0.47, respectively, in PCOS patients. A two fold higher FAI value was observed in metabolic PCOS phenotype when compared to the reproductive one (8.51 ± 5.56 vs. 4.40 ± 2.45 for HOMA-IR and 8.73 ± 6.09 vs. 4.31 ± 3.39 for FI, respectively; p < 0.05). Conclusions: PCOS patients are not a homogenous group in terms of FAI value. Patients with metabolic PCOS phenotype are characterised by twofold higher FAI values compared with reproductive PCOS phenotype. Further studies on the metabolic and androgenic status of different types of PCOS phenotypes should be carried out.
Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.
The occurrence of focal lesions in the thyroid gland affects up to 65% of the general population, and an important element of diagnostics is the most precise possible distinction between benign and malignant lesions. Despite advanced knowledge and developed algorithms, in some cases the decision to proceed further may cause problems even for an experienced clinician. A promising tool in estimating oncological risk is sonoelastography. This article aims to approximate and organize knowledge in this field in relation to focal lesions of the thyroid gland and to encourage the implementation of the method in everyday practice.
Background Depending on metabolic profile, two different PCOS phenotypes may be distinguished- the metabolic phenotype related to insulin resistance (IR) and the reproductive one, with persistent insulin sensitivity. Hyperandrogenemia, the main feature of PCOS, leads to increased visceral fat and muscle masses and thus to lower insulin sensitivity. In turn, IR leads to metabolic consequences and hormonal imbalance. Moreover, vitamin D deficiency, which is common in PCOS patients, is also associated with insulin resistance. Aim To compare the hormonal profiles and vitamin D status in women with PCOS depending on insulin sensitivity status. Materials and methods One thousand three hundred women with PCOS, aged 18 to 40, were recruited. The patients were divided into two groups depending on their insulin sensitivity status. Metabolic and hormonal parameters were assessed in subjects from each group. Blood samples were collected between the second and the sixth day of the menstrual cycle (follicular phase)for the quantification of hormonal parameters using the electrochemiluminescence immunoassay (ECLIA) methods or colorimetry. Results Patients with insulin resistance have a significantly higher concentration of DHEAS and TSH, higher Free Androgen Index, and significantly lower vitamin D concentration. Moreover, cortisol and estradiol concentrations are higher and prolactin is lower in patients with IR, but the differences are not statistically significant. There are no significant differences in the prevalence of Hashimoto disease between patients with IR and patients with persistent insulin sensitivity. Conclusions Metabolic phenotype of PCOS is associated with higher androgen concentration and higher TSH concentration compared to reproductive phenotype. Moreover, patients with PCOS and IR often have vitamin D deficiency compared to patients with persistent insulin sensitivity. Therefore the supplementation of vitamin D and regular TSH measurements are important in patients with metabolic PCOS phenotype. Presentation: No date and time listed
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